松果腺对血清皮质酮的影响及其作用部位分析

松果腺对血清皮质酮有抑制作用，对其昼夜节律的中值及峰值位相亦产生影响．松果腺抑制肾上腺增重，切除松果腺使血浆ＡＣＴＨ升高，注射地塞米松或戊巴比妥钠均阻断了松果腺激素褪黑素的降皮质酮作用。提示：松果腺对血清皮质酮的抑制作用是通过其激素——褪黑素实现的，而褪黑素则主要是通过下丘脑－垂体－肾上腺皮质轴起的作用．     

Evaluating a new approach to selecting medical students

Summary. Dissatisfaction with the traditional methods of selecting Australian medical students, which use only secondary school achievement, led to an innovative alternative method at the Newcastle Medical School. This multistage approach uses tests of problem-solving ability, empathy, creativity and moral dilemmas to screen applicants otherwise suitable on academic achievement. In the 5-year trial since its inception, this process appears reasonably reliable and valid. There is some merit in using a composite score for ranking applicants, based on weighted contributions from the psychological tests used in its multifactorial battery. However, the ultimate effectiveness of individual tests of a composite score will depend on their predictive validity, which is yet unmeasured.     

Corneal sensitivity in myasthenia gravis.

Corneal touch thresholds were measured in 11 people suffering from myasthenia gravis (MG) and in a control group of 20 subjects. The mean threshold in MG was 75.6 mg (SD 52) and in the control group 18.9 mg (SD 7.3); thresholds were thus significantly (p less than 0.01) raised in MG. Although it is not possible to say whether the sensory deficit is due to MG or to the treatment, the results implicate acetylcholine in sensory transduction in the cornea.     

Can anaerobic threshold be used as an end-point for therapeutic trials in heart failure?: Lessons from a multicentre randomized placebo-controlled trial

‘Anaerobic threshold’ (AT), proposed as a non-invasiveindex of exercise tolerance, independent of patient motivation,is considered more reliable than exercise duration in assessingthe effect of drug therapy in chronic heart failure (CHF). However,inter-observer variation in patients may be more difficult thanin normal subjects. In a multicentre study, 85 patients from10 centres performed a total of 331 bicycle maximal tests (rampprotocols, 10 watts. min^–1) with respiratory gas analysisby different systems. A central committee reviewed all the tests.Percentages of AT determination ranged from 34% to 71% dependingon the method used. Apart from the respiratory exchange ratio(RER=1) method, which yielded the lowest rate of determination.and the crossing point (when RER=1), which yielded the highestrate, 71%, other methods of determination, such as carbon dioxide(42%), minute ventilation (52%) or ventilatory equivalents plottedvs time (57%), did not dtffer in the rate of AT determination. Thus, even among trained physicians, AT determination was notreliable. The crossing point may nevertheless be a valuableindex from a pragmatic standpoint, although it occurs afterthe actual AT Peak oxygen uptake should remain the main end-pointin assessment of exercise capacity.     

Leukocyte-technetium-99m uptake in Crohn’s disease: Does it show subclinical disease?

AIM: To evaluate inflammatory activity in patients with Crohn’s disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn’s Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes.RESULTS: The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% ± 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20).CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.     

A prospective surveillance study of factor VIII inhibitor development in the Canadian haemophilia A population following the switch to a recombinant factor VIII product formulated with sucrose

Summary.  The introduction of new factor concentrates has, at times, resulted in an increase in inhibitor development; hence large systematic surveys of inhibitor development are necessary whenever new products are introduced. This study presents the results of a surveillance study conducted by the Inhibitor Subcommittee of the Association of Hemophilia Clinic Directors of Canada that evaluated inhibitor development in patients with haemophilia A following the switch to a second generation recombinant FVIII product (rFVIII-FS; Kogenate^® Bayer). Four hundred and sixty haemophilia A paediatric and adults patients from 17 Canadian Comprehensive Hemophilia Care Centers were enrolled in the study. Of these, 274 patients had evaluable data. Blood samples collected at baseline (prior to the switch to rFVIII-FS), and at 12 and 24 months following conversion were tested for inhibitors by the Nijmegen-modified Bethesda assay. Four subjects had positive inhibitor titres at baseline, with values ranging from 3.3 to 160 BU. Of the 274 patients who had baseline samples collected, 225 had postswitch samples collected at 12 months and 189 subjects had samples collected at 24 months. Only patients with positive baseline inhibitor titres ( n  = 4) had positive inhibitor titres at either the 12- or 24-month postswitch time points; therefore no de novo inhibitors developed over the 2-year evaluation period in this patient population. The results of this surveillance study suggest that the altered formulation of this recombinant FVIII concentrate was not associated with an increased incidence of inhibitor formation.     

Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples

OBJECTIVE: To determine whether the diagnosis of lupus anticoagulant (LAC) in a large cohort of positive patients was confirmed at a reference laboratory. METHODS: Over a 1-year period, each participating center collected samples from LAC-positive patients. Plasma was filtered and kept deep-frozen until it was sent on dry ice to the reference laboratory by express courier. Centers returned detailed laboratory information and clinical data from each patient. The reference laboratory screened plasma samples by diluted Russell viper venom time (dRVVT) and kaolin clotting time (KCT). When these were prolonged, 1:1 mixing studies were carried out, and confirmatory tests were performed as appropriate. Positive samples were further tested by thrombin time (TT). The presence of heparin was checked by measuring antifactor Xa activity when TT was prolonged. Negative samples were tested by activated partial thromboplastin time using hexagonal phospholipids. RESULTS: Plasma samples from 302 patients from 29 anticoagulation clinics were analyzed. LAC was excluded in 71 samples (24%), because dRVVT and KCT screening test results were normal (34) or reversed to normal by mixing studies (35). The remaining two samples were considered negative because they contained heparin. LAC-negative patients showed different characteristics from those in whom diagnosis was confirmed. They were significantly older (49.7 vs. 45.0 years, P < 0.03), were more often first diagnosed (66% vs. 41%, P < 0.001), and were more frequently judged as mild in LAC potency (60% vs. 25%, P < 0.0001). Moreover, anticardiolipin and anti-beta(2)-glycoprotein I antibody values were more often normal in LAC-negative (82%) than in LAC-positive (42%) samples (P < 0.0001). LAC-positive samples identified by both dRVVT and KCT (146/231, 63%) showed a LAC potency that was significantly stronger than that in samples in which LAC diagnosis was made by a single test. CONCLUSIONS: A false-positive LAC diagnosis is not uncommon across specialized centers. Patients' characteristics and a complete antiphospholipid antibody profile may help to identify these individuals.     

Meeting Report: Ninth and Tenth Workshops of the European Paediatric Network for Haemophilia Management (PedNet)

This meeting report presents an overview of the discussions at the ninth and tenth workshops of the European Paediatric Network for Haemophilia Management (PedNet) that occurred in 2005 and 2006. Among numerous topics, a major theme of these workshops was the formation of inhibitors to replacement factor.     

Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A

Recent reports have suggested that the incidence of inhibitors in haemophilia is the highest in those first exposed to factor VIII under 6 months of age. In this study, we investigated inhibitor development in children first exposed to FVIII as neonates and also examined the effect of other genetic and environmental variables. Three hundred and forty-eight children with severe haemophilia A were investigated. Inhibitors developed in 68 of 348 (20%), with 34 of 348 (10%) high titre inhibitors. The incidence in relation to initial FVIII exposure was: <1 month nine of 35 (26%), 1-6 months 13 of 51 (25%), 6-12 months 27 of 130 (21%), 12-18 months 13 of 66 (20%) and >18 months six of 66 (9%). While we observed a significant difference in inhibitor development and age at first exposure across all age groups (P = 0.018), no significant difference was observed in children treated at different time points during the first year of life (P = 0.44). Similar results were obtained for high titre inhibitors. There was also no difference in the incidence of inhibitors in relation to initial FVIII exposure in a subgroup of 144 children with the intron 22 mutation. Inhibitors developed more frequently in those initially treated with recombinant when compared with plasma-derived FVIII (P = 0.006) and in those with a major molecular defect (P = 0.009). In this study, exposure to FVIII during the neonatal period was not associated with a higher incidence of inhibitors than those treated later during the first year of life. Initial treatment with recombinant FVIII and the presence of a major molecular defect were the most important variables affecting inhibitor development.